Abstract
Isolated or cultured cells have proven to be valuable model systems to investigate cellular (patho)biology and for screening of the efficacy of drugs or their possible side-effects. Pluripotent stem cells (PSC) can be readily obtained from healthy individuals as well as from diseased patients, and protocols have been developed to differentiate these cells into cardiomyocytes. Hence, these cellular models are moving center stage for a broader application. In this review, we focus on comparing mouse HL-1 cardiomyocytes, isolated adult rat cardiomyocytes, human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for the study of metabolic aspects of cardiac functioning in health and disease. Various studies have reported that these cellular models are suitable for assessing substrate uptake and utilization, in that each display an adequate and similar response to physiological triggers, in particular the presence of insulin. Likewise, disease conditions, such as excess lipid supply, similarly affect each of these rodent and human cardiomyocyte models. It is concluded that PSC-CMs obtained from patients with cardiogenetic abnormalities are promising models to evaluate the functional consequence of gene variants with unknown significance.
Highlights
The enduring availability of sufficient chemical energy, in the form of ATP, is vital for proper cardiac function
We compared mouse HL-1 cardiomyocytes, isolated rat cardiomyocytes, hESC-CMs, and hiPSC-CMs for their suitability to be used for the assessment of dynamic metabolic parameters with focus on the regulation of insulin signaling by lipids
Under disease conditions, in particular high lipidinduced insulin resistance, the changes in substrate utilization, and insulin signaling were similar among the model systems
Summary
The enduring availability of sufficient chemical energy, in the form of ATP, is vital for proper cardiac function. When obtained from patients suffering from (genetic) cardiac disease, the hiPSC-CMs can be applied for evaluating whether the genetic abnormality is causal to the disease phenotype [10,11]. These cells can be applied for screening of drugs that would be effective for treatment while having limited side-effects [12]. We will focus on lipid-induced insulin resistance and con tractile dysfunction for which the underlying mechanistic changes are outlined in the paragraph below From this evaluation it is concluded that, in general, metabolic aspects of cardiovascular disease can be studied well in these rodent and human model systems. The consequences of this observation for the application of these model systems are discussed
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